The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and hypoxia-inducible factor 1-alpha.

BACKGROUND: Acute myeloid leukemia (AML), a malignancy Often resistant to common chemotherapy regimens (Cytarabine (Ara-c) + Daunorubicin (DNR)), is accompanied by frequent relapses. Many factors are involved in causing chemoresistance. Heme Oxygenase-1 (HO-1) and Hypoxia-Inducible Factor 1-alpha (HIF-1α) are two of the most well-known genes, reported to be overexpressed in AML and promote resistance against chemotherapy according to several studies. The main chemotherapy agent used for AML treatment is Ara-c. We hypothesized that simultaneous targeting of HO-1 and HIF-1α could sensitize AML cells to Ara-c. METHOD: In this study, we used our recently developed, Trans-Activator of Transcription (TAT) - Chitosan-Carboxymethyl Dextran (CCMD) - Poly Ethylene Glycol (PEG) - Nanoparticles (NPs), to deliver Ara-c along with siRNA molecules against the HO-1 and HIF-1α genes to AML primary cells (ex vivo) and cell lines including THP-1, KG-1, and HL-60 (in vitro). Subsequently, the effect of the single or combinational treatment on the growth, proliferation, apoptosis, and Reactive Oxygen Species (ROS) formation was evaluated. RESULTS: The designed NPs had a high potential in transfecting cells with siRNAs and drug. The results demonstrated that treatment of cells with Ara-c elevated the generation of ROS in the cells while decreasing the proliferation potential. Following the silencing of HO-1, the rate of apoptosis and ROS generation in response to Ara-c increased significantly. While proliferation and growth inhibition were considerably evident in HIF-1α-siRNA-transfected-AML cells compared to cells treated with free Ara-c. We found that the co-inhibition of genes could further sensitize AML cells to Ara-c treatment. CONCLUSIONS: As far as we are aware, this study is the first to simultaneously inhibit the HO-1 and HIF-1α genes in AML using NPs. It can be concluded that HO-1 causes chemoresistance by protecting cells from ROS damage. Whereas, HIF-1α mostly exerts prolific and direct anti-apoptotic effects. These findings imply that simultaneous inhibition of HO-1 and HIF-1α can overcome Ara-c resistance and help improve the prognosis of AML patients.

Synthesis of metformin-derived fluorescent quantum dots: uptake, cytotoxicity, and inhibition in human breast cancer cells through autophagy pathway.

BACKGROUND: Breast cancer remains a challenge for physicians. Metformin, an antidiabetic drug, show promising anticancer properties against cancers. An emerging quantum dot (QD) material improves therapeutic agents' anticancer and imaging properties. QD are nano-sized particles with extreme application in nanotechnology captured by cells and accumulated inside cells, suggesting bioimaging and effective anticancer outcomes. In this study, a simple one-pot hydrothermal method was used to synthesize fluorescent metformin-derived carbon dots (M-CDs) and then investigated the cytotoxic effects and imaging features on two human breast cancer cell lines including, MCF-7 and MDA-MB-231 cells. RESULTS: Results showed that M-CDs profoundly decreased the viability of both cancer cells. IC50 values showed that M-CDs were more cytotoxic than metformin either 24-48 h post-treatment. Cancer cells uptake M-CDs successfully, which causes morphological changes in cells and increased levels of intracellular ROS. The number of Oil Red O-positive cells and the expression of caspase-3 protein were increased in M-CDs treated cells. Authophagic factors including, AMPK, mTOR, and P62 were down-regulated, while p-AMPK, Becline-1, LC3 I, and LC3 II were up-regulated in M-CDs treated cells. Finally, M-CDs caused a decrease in the wound healing rate of cells. CONCLUSIONS: For the first, M-CDs were synthesized by simple one-pot hydrothermal treatment without further purification. M-CDs inhibited both breast cancer cells through modulating autophagy signalling.

Polydopamine contained hydrogel nanocomposites with combined antimicrobial and antioxidant properties for accelerated wound healing.

Overproduction of reactive oxygen species (ROS) in infected wounds induces a tremendous inflammatory reaction to delay wound healing. To address this problem, we designed a multifunctional polyacrylamide/PVA-based hydrogel containing synthesized poly(1-glycidyl-3-butylimidazolium salicylate) (polyGBImSal) and fabricated polydopamine-coated polyphenolic nanosheet (PDA@PNS) for wound dressing. The PDA@PNS particles were designed to induce I) antioxidant and anti-inflammatory features through ROS-scavenging and II) cell adhesive properties by the existing polydopamine into the hydrogels. The poly(ionic liquid)-based polyGBImSal was designed to allocate effective hydrogel antimicrobial activity. The fabricated hydrogel nanocomposites showed excellent properties in the swelling ratio, cell adhesiveness, protein adsorption, and anti-inflammatory, proving their general performance for application in wound healing. Furthermore, these hydrogels showed high antimicrobial activity (over 95 %) against three common wound-infecting pathogenic microbes: Escherichia coli, Staphylococcus aureus, and Candida albicans. The healing process of full-thickness dermal wounds in rats was accelerated by applying hydrogel nanocomposites with 0.5 wt% of PDA@PNS and 28 wt% of polyGBImSal. The wound closure contraction attained full closure, reaching 100 %, after 14 days, contrasted with the control group employing commercial wound dressing (Tegaderm), which achieved a closure rate of 68 % within the equivalent timeframe. These results make these hydrogel nanocomposites promising candidates for multifunctional wound dressing applications.

Insights into the effects of anthropogenic activities on oil reservoir microbiome and metabolic potential.

Microbial communities have long been observed in oil reservoirs, where the subsurface conditions are major drivers shaping their structure and functions. Furthermore, anthropogenic activities such as water flooding during oil production can affect microbial activities and community compositions in oil reservoirs through the injection of recycled produced water, often associated with biocides. However, it is still unclear to what extent the introduced chemicals and microbes influence the metabolic potential of the subsurface microbiome. Here we investigated an onshore oilfield in Germany (Field A) that undergoes secondary oil production along with biocide treatment to prevent souring and microbially induced corrosion (MIC). With the integrated approach of 16 S rRNA gene amplicon and shotgun metagenomic sequencing of water-oil samples from 4 production wells and 1 injection well, we found differences in microbial community structure and metabolic functions. In the injection water samples, amplicon sequence variants (ASVs) belonging to families such as Halanaerobiaceae, Ectothiorhodospiraceae, Hydrogenophilaceae, Halobacteroidaceae, Desulfohalobiaceae, and Methanosarcinaceae were dominant, while in the production water samples, ASVs of families such as Thermotogaceae, Nitrospiraceae, Petrotogaceae, Syntrophaceae, Methanobacteriaceae, and Thermoprotei were also dominant. The metagenomic analysis of the injection water sample revealed the presence of C1-metabolism, namely, genes involved in formaldehyde oxidation. Our analysis revealed that the microbial community structure of the production water samples diverged slightly from that of injection water samples. Additionally, a metabolic potential for oxidizing the applied biocide clearly occurred in the injection water samples indicating an adaptation and buildup of degradation capacity or resistance against the added biocide.

Nonoperative management of biliopleural fistula following living-donor liver transplantation: A case report.

Key Clinical Message: Biliopleural fistula is a rare but serious complication after liver transplantation that should be managed nonoperatively with antibiotics, pleural drainage, decompression of high-pressure biliary tract, or ultimately surgery in unresponsive cases. Abstract: Bilious pleural effusion is a rare entity often iatrogenic, following hepatobiliary surgeries and biliary interventions, and has been reported only in a limited number of patients after liver transplantation. A 5-year-old girl underwent living donor liver transplantation due to progressive familial intrahepatic cholestasis. At the 7th day of the postoperative course, due to increased liver enzymes and bilirubin levels and intrahepatic bile duct dilatation on sonography, Magnetic Resonance Cholangiopancreaticography followed by a liver biopsy were performed; the findings demonstrated moderate intrahepatic bile duct dilatation and moderate cellular rejection associated with mild cholestasis, respectively. The patient was therefore administered a pulse of methylprednisolone; however, due to fever, peritonitis and also sonographic evidence of infected biloma collection adjacent to the transplanted liver, the patient underwent surgery. Laparotomy and peritoneal washout were performed and a Jackson-Pratt drain was inserted adjacent to the liver cut surface. Succeeding tachypnea on 28th post day, led to detection of right side massive pleural effusion on chest Xray and hence thoracostomy tube was inserted. A diagnosis of biliopleural fistula was established and broad-spectrum intravenous antibiotic therapy was started, followed by cholangiography, fistula closure, and bile duct stricture ballooning and internal-external biliary catheter insertion. The patient was discharged in generally good condition on the 50th posttransplant day. The diagnosis of biliopleural fistula is facilitated with the utilization of chest imaging and pleural fluid analysis, however, a high index of suspicion is required.

Recent Advances in Functional Cellulose-based Films with Antimicrobial and Antioxidant Properties for Food Packaging.

The packaging of food plays a crucial role in food preservation worldwide. However, traditional packaging systems are passive layers with weak efficiency in protecting the food quality. Therefore, packaged foods are gradually spoiled due to the oxidation and growth of microorganisms. Additionally, most of the commercial packaging films are made of petroleum-based materials which raise environmental concerns. Accordingly, the development of eco-friendly natural-derived active packaging systems has increased the attention of scientists. Cellulose as the most abundant polysaccharide on earth with high biocompatibility, no toxicity, and high biodegradability has extensively been applied for the fabrication of packaging films. However, neat cellulose-based films lack antioxidant and antimicrobial activities. Therefore, neat cellulose-based films are passive films with weak food preservation performance. Active films have been developed by incorporating antioxidants and antimicrobial agents into the films. In this review, we have explored the latest research on the fabrication of antimicrobial/antioxidant cellulose-based active packaging films by incorporating natural extracts, natural polyphenols, nanoparticles, and microparticles into the cellulose-based film formulations. We categorized these types of packaging films into two main groups: (i) blend films which are obtained by mixing solutions of cellulose with other soluble antimicrobial/antioxidant agents such as natural extracts and polyphenols; and (ii) composite films which are fabricated by dispersing antimicrobial/antioxidant nano- or microfillers into the cellulose solution. The effect of these additives on the antioxidant and antimicrobial properties of the films has been explained. Additionally, the changes in the other properties of the films such as hydrophilicity, water evaporation rate, and mechanical properties have also been briefly addressed.

Acute or Short-term Effects of Whey Protein Alone or Along with Carbohydrate on Inflammation: A Systematic Review of Clinical Trials:.

BACKGROUND: Excessive inflammatory response is associated with several diseases. Recently, there has been an increasing trend for investigation of the acute or short-term effects of whey protein alone or in combination with carbohydrates on inflammatory status, especially in athletes. This systematic review aimed to clarify these effects. MATERIALS AND METHODS: PubMed, Scopus, and Web of Science databases were searched from January 1990 to September 2021, without language restriction. Adult studies examining the effects of whey protein alone or together with carbohydrates on interleukin-6, tumor necrosis factor-α, and C-reactive protein levels with a maximum duration of 15 days and with at least one comparison group were included. The quality of studies was analyzed using the Cochrane risk of bias tool. RESULTS: Twenty-five studies met the inclusion criteria. Significant reductions in inflammatory markers was observed in seven out of 25 studies (28%). However, one out of 25 studies (4%) reported a significant increase in inflammatory status. Among those studies comparing the effects of whey protein alone with non-protein or protein-containing groups, 18.18% (two out of 11) and 10% (one out of ten) of the trials revealed a significant decrease in the markers, respectively. Moreover, of those studies comparing whey protein plus carbohydrate with non-protein or protein-containing groups, 33.33% (two out of six) and 40% (two out of five) of them showed a significant reduction in the inflammatory response, respectively. The quality of the majority of studies (84%) was poor. CONCLUSION: It seems that whey protein alone or the combination of it with carbohydrates may not affect the inflammatory markers in the short run (PROSPERO registration number: CRD42021273915).[GMJ.2023;12:e2441].

Investigation of L-carnitine effects on CD44+ cancer stem cells from MDA-MB-231 breast cancer cell line as anti-cancer therapy.

Breast cancer stem cells (BCSCs) are a small subpopulation of breast cancer cells, capable of metastasis, recurrence, and drug resistance in breast cancer patients. Therefore, targeting BCSCs appears to be a promising strategy for the treatment and prevention of breast cancer metastasis. Mounting evidence supports the fact that carnitine, a potent antioxidant, modulates various mechanisms by enhancing cellular respiration, inducing apoptosis, and reducing proliferation and inflammatory responses in tumor cells. The objective of this study was to investigate the impact of L-carnitine (LC) on the rate of proliferation and induction of apoptosis in CD44+ CSCs. To achieve this, the CD44+ cells were enriched using the Magnetic-activated cell sorting (MACS) isolation method, followed by treatment with LC at various concentrations. Flow cytometry analysis was used to determine cell apoptosis and proliferation, and western blotting was performed to detect the expression levels of proteins. Treatment with LC resulted in a significant decrease in the levels of p-JAK2, p-STAT3, Leptin receptor, and components of the leptin pathway. Moreover, CD44+ CSCs-treated cells with LC exhibited a reduction in the proliferation rate, accompanied by an increase in the percentage of apoptotic cells. Hence, it was concluded that LC could potentially influence the proliferation and apoptosis of CD44+ CSC by modulating the expression levels of specific protein.

Putrescine-functionalized carbon quantum dot (put-CQD) nanoparticle: A promising stress-protecting agent against cadmium stress in grapevine (Vitis vinifera cv. Sultana).

Due to their sessile nature, plant cannot escape from stress factors in their growing environment, in either biotic or abiotic nature. Amid the abiotic stress factors; high levels of soil cadmium (Cd) impose heavy metal stress on plants, resulting in critical injuries and reduced agronomic performance. In order to buffer the adverse effects of Cd stress, novel nanoparticles (NP) have been applied and notable improvements have been reported. According to the literature, the protective roles of polyamines (e.g., Putrescine; Put) and carbon quantum dots (CQD) have been reported with respect to the plant productivity under either stress or non-stress conditions. Those reports led us to hypothesize that the conjugation of Put and CQD (Put-CQD NPs) might lead to further augmented performance of plants under stress and non-stress conditions. In this regard, we successfully synthesized a novel nanomaterial Put-CQD NPs. In this respect, Put (50 mg L-1), CQD (50 mg L-1) and Put-CQD NPs (25 and 50 mg L-1) were sprayed in 'Sultana' grapevines under Cd stress (10 mg kg-1). As expected, upon stress, Cd content in leaf and root tissues increased by 103.40% and 65.15%, respectively (p < 0.05). The high uptake and accumulation of Cd in plant tissues were manifested in significant alterations of physiological and biochemical attributes of the plant. Concerning stress markers, Cd stress caused increases in content of induced MDA, H2O2, and proline as well as electrolyte leakage rate. As expected, Cd stress caused critical reductions in fresh and dry leaf weight by 21.31% and 42.34%, respectively (p < 0.05). On the other hand, both Put-CQD NPs increased fresh and dry leaf weigh up to approximately 30%. The Cd-mediated disturbances in photosynthetic pigments and chlorophyll fluorescence were buffered with Put-CQD NPs. Of the defence system, enzymatic (SOD, APX, GP) as well as anthocyanin and phenolics were induced by both Cd stress and Put-CQD NPs (p < 0.05). On the other hand, Cd stress reduced content of polyamines (putrescine (Put), spermine (Spm) and spermidine (Spd) by 39.28%, 53.36%, and 39.26%, respectively (p < 0.05). However, the reduction levels were buffered by the treatments. Considering the effectiveness of both NP concentrations, the lower dose (25 mg L-1) could be considered as an optimal concentration. To our knowledge, this is the first report of its kind as a potential agent to reduce the adverse effects of Cd stress in grapevines.

The prognostic and therapeutic potential of HO-1 in leukemia and MDS.

BACKGROUND: Heme oxygenase-1 (HO-1), a heme-degrading enzyme, is proven to have anti-apoptotic effects in several malignancies. In addition, HO-1 is reported to cause chemoresistance and increase cell survival. Growing evidence indicates that HO-1 contributes to the course of hematological malignancies as well. Here, the expression pattern, prognostic value, and the effect of HO-1 targeting in HMs are discussed. MAIN BODY: According to the recent literature, it was discovered that HO-1 is overexpressed in myelodysplastic syndromes (MDS), chronic myeloid leukemia (CML), acute myeloblastic leukemia (AML), and acute lymphoblastic leukemia (ALL) cells and is associated with high-risk disease. Furthermore, in addition to HO-1 expression by leukemic and MDS cells, CML, AML, and ALL leukemic stem cells express this protein as well, making it a potential target for eliminating minimal residual disease (MRD). Moreover, it was concluded that HO-1 induces tumor progression and prevents apoptosis through various pathways. CONCLUSION: HO-1 has great potential in determining the prognosis of leukemia and MDS patients. HO-1 induces resistance to several chemotherapeutic agents as well as tyrosine kinase inhibitors and following its inhibition, chemo-sensitivity increases. Moreover, the exact role of HO-1 in Chronic Lymphocytic Leukemia (CLL) is yet unknown. While findings illustrate that MDS and other leukemic patients could benefit from HO-1 targeting. Future studies can help broaden our knowledge regarding the role of HO-1 in MDS and leukemia. Video abstract.

ARID1B, a molecular suppressor of erythropoiesis, is essential for the prevention of Monge's disease.

At high altitude Andean region, hypoxia-induced excessive erythrocytosis (EE) is the defining feature of Monge's disease or chronic mountain sickness (CMS). At the same altitude, resides a population that has developed adaptive mechanism(s) to constrain this hypoxic response (non-CMS). In this study, we utilized an in vitro induced pluripotent stem cell model system to study both populations using genomic and molecular approaches. Our whole genome analysis of the two groups identified differential SNPs between the CMS and non-CMS subjects in the ARID1B region. Under hypoxia, the expression levels of ARID1B significantly increased in the non-CMS cells but decreased in the CMS cells. At the molecular level, ARID1B knockdown (KD) in non-CMS cells increased the levels of the transcriptional regulator GATA1 by 3-fold and RBC levels by 100-fold under hypoxia. ARID1B KD in non-CMS cells led to increased proliferation and EPO sensitivity by lowering p53 levels and decreasing apoptosis through GATA1 mediation. Interestingly, under hypoxia ARID1B showed an epigenetic role, altering the chromatin states of erythroid genes. Indeed, combined Real-time PCR and ATAC-Seq results showed that ARID1B modulates the expression of GATA1 and p53 and chromatin accessibility at GATA1/p53 target genes. We conclude that ARID1B is a novel erythroid regulator under hypoxia that controls various aspects of erythropoiesis in high-altitude dwellers.

Adherence to a western dietary pattern and risk of invasive ductal and lobular breast carcinomas: a case-control study.

Little is known about the role of diet in the risk of invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast, the most common histological subtypes of breast cancer (BC). This is because, the majority of studies on the association of diet and the risk of BC are focused on single food items, and studies considering the overall diet in terms of dietary patterns are limited. Also, the potential heterogeneity in the impact of Western diet (WD) on histological subtypes of BC is not established. This, the age-frequency-matched case-control study included 1009 incident BC cases and 1009 healthy controls. The required data was obtained from the patients' medical files and interviews using a previously validated researcher-designed questionnaire for collecting data on socio-economic and anthropometric statuses and a valid food frequency questionnaire (FFQ) to measure the participants' dietary intake. We used multinomial logistic regression, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A positive and significant association was observed between higher adherence to a WD and risk of IDC (OR comparing highest with the lowest tertile: 2.45, 95% CI 1.88, 3.17; p-trend < 0.001), whereas no significant association was observed between adherence to the WD and the risk of ILC (OR comparing highest with the lowest tertile: 1.63, 95% CI 0.63, 3.25) (p for heterogeneity = 0.03). The results of an analysis stratified by menopausal status suggested a similar pattern. We provided evidence that adherence to a WD raises the risk of IDC, but not ILC, suggesting different etiological mechanisms for IDC and ILC.

Inhibition of extracellular vesicle biogenesis in tumor cells: A possible way to reduce tumorigenesis.

Most eukaryotic cells secrete extracellular vesicles (EVs), which contribute to intracellular communication through transferring different biomolecules such as proteins, RNAs, and lipids to cells. Two main types of EVs are exosomes and microvesicles. Exosomes originate from multivesicular bodies, while microvesicles are shed from the plasma membrane. Mechanisms of exosomes and microvesicle biogenesis/trafficking are complex and many molecules are involved in their biogenesis and secretion. Tumor-derived EVs contain oncogenic molecules that promote tumor growth, metastasis, immune surveillance, angiogenesis, and chemoresistance. A growing body of evidence indicates various compounds can inhibit biogenesis and secretion of EVs from cells and several experiments were conducted to use EVs-inhibitors for understanding the biology of the cells or for understanding the pathology of several diseases like cancer. However, the nontargeting effects of drugs/inhibitors remain a concern. Our current knowledge of EVs biogenesis and their inhibition from tumor cells may provide an avenue for cancer management. In this review, we shed light on exosomes and microvesicles biogenesis, key roles of tumor-derived EVs, and discuss methods used to inhibition of EVs by different inhibitors.

Dietary patterns and risk of bladder cancer: a systematic review and meta-analysis.

BACKGROUND: Several studies have investigated the relationship between dietary patterns and the risk of bladder cancer (BC) in different regions including Europe, the United States, and Asia, with no conclusive evidence. A meta-analysis was undertaken to integrate the most recent information on the relationship between a data-driven Western diet (WD), the Mediterranean diet (MD), and dietary-inflammatory-index (DII) and the risk of BC. METHOD: We looked for published research into the relationship between dietary patterns and the incidence of BC in the PubMed/Medline, Cochrane Library, Web of Science, and Scopus databases up until February 2021. Using a multivariate random-effects model, we compared the highest and lowest categories of WD, MD and DII patterns and provided the relative risk (RR) or odds ratios (OR) and 95 percent confidence intervals (CIs) for the relevant relationships. RESULTS: The analysis comprised 12 papers that were found to be suitable after scanning the databases. Both case-control (OR 0.73, 95% CI: 0.52, 0.94; I2 = 49.9%, n = 2) and cohort studies (RR 0.93, 95% CI: 0.88, 0.97; I2 = 63%, n = 4) found a substantial inverse association between MD and BC. In addition, although cohort studies (RR 1.53, 95% CI 1.37, 1.70; I2 = 0%, n = 2) showed a direct association between WD and BC, case-control studies (OR 1.33, 95% CI 0.81, 1.88; I2 = 68.5%, n = 2) did not. In cohort studies, we found no significant association between DII and BC (RR 1.02, 95% CI 0.93, 1.12; I2 = 38.5%, n = 2). In case-control studies, however, a strong direct association between DII and BC was discovered (RR 2.04, 95% CI 1.23, 2.85; I2 = 0%, n = 2). CONCLUSION: The current meta-analysis showed that MD and WD have protective and detrimental effects on BC risk, respectively. No significant association between DII and the risk of BC was observed. More research is still needed to confirm the findings. Additional study is warranted to better understand the etiological mechanisms underlying how different dietary patterns affect BC. TRIAL REGISTRATION: Protocol registration number: CRD42020155353. Database for protocol registration: The international prospective register of systematic reviews database (PROSPERO). Data of registration: August 2020.

Outcomes in Severe COVID-19 Patients Following Percutaneous Versus Open Surgical Tracheostomy: An Analysis of Clinical and Prognostic Indicators.

Background and objective Tracheostomy in coronavirus disease 2019 (COVID-19) patients can be performed in cases of prolonged intubation or in patients with a known difficult airway. Tracheostomy is usually performed by two main approaches: open surgery or percutaneous endoscopic insertion. However, few studies have compared these two techniques in severe COVID-19 patients. The objective of the present study was to compare the efficacy of the two main methods of tracheostomy among patients with severe COVID-19 infection. We also aimed to investigate the impact of various lab data and medications on patient outcomes. Materials and methods We included all symptomatic severe COVID-19 patients in need of prolonged mechanical ventilation. We examined the patients' past medical history, arterial blood gas (ABG) analysis, laboratory workups, and medication history. We calculated the PaO2/FiO2 ratio as an index to evaluate the severity of acute respiratory distress syndrome (ARDS). Results During the study period, 72 patients with severe COVID-19 underwent tracheostomy tube insertion. The average age of participants was 58.93 ±15.27 years; 44 (61.1%) were male and 28 (38.9%) were female. Of note, 54 (75.0%) patients passed away and only 18 (25.0%) survived. Among the survivors, 13 (29.5%) were men and five (17.9%) were women. The study showed a significantly higher mortality rate (23, 92.0%) among patients who underwent open surgery compared to those who received percutaneous surgery (31, 65.9%) (p=0.01). Conclusion Based on our findings, percutaneous endoscopic tracheostomy seems to be the superior approach compared to open tracheostomy. Other predictive factors associated with patient outcomes included levels of HCO3, FiO2, PaCO2, and PaO2/FiO2 ratio.

Engineered Exosomes for Tumor-Targeted Drug Delivery: A Focus on Genetic and Chemical Functionalization.

Cancer is the main cause of death worldwide. The limitations in traditional cancer therapies provoked the advance and use of several nanotechnologies for more effective and nontoxic cancer treatment. Along with synthetic nanocarriers, extracellular vesicles (EVs)-mediated drug delivery systems have aroused substantial interest. The term EVs refers to cell-derived nanovesicles, such as exosomes, with phospholipid-bound structures, participating in cell-to-cell communication. Exosomes are 30-150 nm vesicles that can transfer many biological molecules between cells. From a drug delivery standpoint, exosomes can be loaded with various therapeutic cargo, with the several advantages of low immunogenicity, high biocompatibility, transformative, and effective tumor targeting aptitude. The exosomal surface can be functionalized to improve tumor targeting ability of them. Researchers have genetically expressed or chemically linked various molecules on the surface of exosomes. Despite extensive investigation, clinical translation of exosome-based drug delivery remains challenging. In this review, we discuss various methods used to loading exosomes with therapeutic cargo. We describe examples of functionalized exosomes surface using genetic and chemical modification methods. Finally, this review attempts to provide future outlooks for exosome-based targeted drug delivery.

The prognostic and therapeutic potentials of CTLA-4 in hematological malignancies.

INTRODUCTION: Hematological Malignancies (HMs) are a group of progressive, difficult-to-treat, and highly recurrent diseases. A suppressed phenotype of the immune system is present in HMs and growing evidence indicates the role of Cytotoxic T lymphocyte-Associated protein 4 (CTLA-4) in the course of HMs. AREAS COVERED: This article reviews the recent literature on the role of CTLA-4 in different subtypes of HMs. Here, the studies on the expression pattern, its effect on the prognosis of different HMs, and polymorphisms of CTLA-4 have been elaborated. Finally, the effect of targeting CTLA-4 in vitro and in vivo, as well as in clinical trials, is discussed. EXPERT OPINION: According to the recent literature, CTLA-4 is overexpressed in different HMs, which is correlated with poor survival, while it is associated with better a prognosis in Chronic Lymphocytic Leukemia (CLL). Targeting CTLA-4 in Acute Myeloid Leukemia (AML), Sezary Syndrome (SS), Hodgkin's Lymphoma (HL), and so on, is helpful. While this is not recommended and may even be harmful in multiple myeloma (MM) and CLL. Also, it seems that certain CTLA-4 gene polymorphisms are efficient factors in the course of HMs. Future studies may broaden our knowledge regarding the role of CTLA-4 in HMs.

Indigenous microbial communities in heavy oil show a threshold response to salinity.

Microbial degradation influences the quality of oil resources. The environmental factors that shape the composition of oil microbial communities are largely unknown because most samples from oil fields are impacted by anthropogenic oil production, perturbing the native ecosystem with exogenous fluids and microorganisms. We investigated the relationship between formation water geochemistry and microbial community composition in undisturbed oil samples. We isolated 43 microliter-sized water droplets naturally enclosed in the heavy oil of the Pitch Lake, Trinidad and Tobago. The water chemistry and microbial community composition within the same water droplet were determined by ion chromatography and 16S rRNA gene amplicon sequencing, respectively. The results revealed a high variability in ion concentrations and community composition between water droplets. Microbial community composition was mostly affected by the chloride concentration, which ranged from freshwater to brackish-sea water. Remarkably, microbial communities did not respond gradually to increasing chloride concentration but showed a sudden change to less diverse and uneven communities when exceeding a chloride concentration of 57.3 mM. The results reveal a threshold-regulated response of microbial communities to salinity, offering new insights into the microbial ecology of oil reservoirs.

Effect of Cellular-Based Artificial Antigen Presenting Cells Expressing ICOSL, in T-cell Subtypes Differentiation and Activation.

Purposes: Effective and selective T-cell activation and proliferation during the T-cell expansion phase of a cellular adoptive immunotherapy method, challenging because recent studies revealed the importance of each subtype of T-cells in different immunologic strategies against tumors, like CAR-T cell therapies. Artificial antigen presenting cells (aAPCs) regarded as a natural way to manipulate T-cell subtypes activation and specific proliferation. In the current study, we utilized K562 cells based aAPC method expressing the ICOSL molecule, to evaluate T-cell subtypes differentiation rate and functional status. Methods: CD3+T-cells isolated and, co-cultured with ICOSL expressing K562 cells. After 4, 6, and 10 days selective CD markers of T-cell subtypes and each subtype's activity-related genes levels evaluated by qPCR methods. Results: During the culture period, CD4+ Th related phenotype reduced continuously, and in day 10th of culture CD4+ T-cell's population significantly reduced (P =0.029). In contrast, the CD8+ population ratio was ascending during the study period but was not statistically significant. FoxP3+CD25-, Treg population ratio was significantly increased during the time in comparison with the control group, as well as memory T-cell phenotypic marker, CD127+, expressing cells ratio. T-cell subpopulations activity-related genes expression levels evaluated too, and the Th1 related IL-2 and INF-γ reductions observed alongside regulatory T-cells gene (IL-10) and Cytotoxic T-cell's related gene (Geranzym-A) elevations. Conclusion: We concluded that the K562-ICOSL based aAPC system is working and effective in T-cell short to medium culture periods, and this approach preparing relatively selective milieu for CD8+ T-Cell differentiation and much less Treg differentiation.

Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells: A Review of Recent Advances.

Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug clearance. Antibodies and ligands targeting the unique factors that maintain the niche are utilized for the delivery of anticancer therapeutics to CSCs. In this regard, nanomaterials, specifically nanoparticles (NPs), are extremely useful as carriers for the delivery of anticancer agents to CSCs. This review covers the biology of CSCs and advances in the design and synthesis of NPs as a carrier in targeting cancer drugs to the CSC subpopulation of cancer cells. This review includes the development of synthetic and natural polymeric NPs, lipid NPs, inorganic NPs, self-assembling protein NPs, antibody-drug conjugates, and extracellular nanovesicles for CSC targeting.